Submit Manuscript  

Article Details


Xiao-Chai-Hu-Tang (XCHT) Intervening Irinotecan’s Disposition: The Potential of XCHT in Alleviating Irinotecan-Induced Diarrhea

[ Vol. 18 , Issue. ]

Author(s):

Rongjin Sun, Sumit Basu, Min Zeng, Robin Sunsong, Li Li, Romi Ghose, Wei Wang, Zhongqiu Liu, Ming Hu* and Song Gao*Pages 1-10 (10)

Abstract:


Background: Diarrhea is a severe side effect of irinotecan, a pro-drug of SN-38 used for the treatment of many types of cancers. Pre-clinical and clinical studies showed that decreasing the colonic exposure of SN-38 can mitigate irinotecan-induced diarrhea. Objective: The purpose of this study is to evaluate the anti-diarrhea potential of Xiao-Chai-Hu-Tang (XCHT), a traditional Chinese herbal formula, against irinotecan-induced diarrhea by determining how XCHT alters the disposition of SN-38. Method: LC-MS/MS was used to quantify the irinotecan and its major metabolites (i.e., SN-38, SN- 38G). An Intestinal perfusion model was used to determine the effect of XCHT on biliary and intestinal secretions of irinotecan, SN-38, and SN-38G. Pharmacokinetic (PK) studies were performed to determine the impact of XCHT on the blood and fecal concentrations of irinotecan, SN-38, and SN- 38G. Results: The results showed that XCHT significantly inhibits both biliary and intestinal excretions of irinotecan, SN-38, and SN-38G (range: 35% to 95%). PK studies revealed that the fecal concentrations of irinotecan and SN-38 were significantly decreased from 818.35 ± 120.2 to 411.74 ± 138.83 μg/g or from 423.95 ± 76.44 to 245.63 ± 56.72 μg/g (p<0.05) by XCHT, respectively, suggesting the colonic exposure of SN-38 is significantly decreased by XCHT. PK studies also showed that the plasma concentrations of irinotecan, SN-38, and SN-38G were not affected by XCHT. Conclusion: In conclusion, XCHT significantly decreased the exposure of SN-38 in the gut without affecting its plasma level, thereby possessing the potential of alleviating irinotecan-induced diarrhea without negatively impacting its therapeutic efficacy.

Keywords:

Xiao-Chai-Hu-Tang, alleviating, Irinotecan, SN-38, disposition, Diarrhea

Affiliation:

International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, Department of Pharmacological and Pharmaceutical Sciences, The University of Houston, 1441 Moursund Street, Houston TX 77030, Department of Pharmacological and Pharmaceutical Sciences, The University of Houston, 1441 Moursund Street, Houston TX 77030, Department of Pharmaceutical and Environmental Sciences, Texas Southern University, 3100 Cleburne Street, Houston TX 77004, Department of Pharmacological and Pharmaceutical Sciences, The University of Houston, 1441 Moursund Street, Houston TX 77030, Department of Pharmacological and Pharmaceutical Sciences, The University of Houston, 1441 Moursund Street, Houston TX 77030, Department of Pharmacological and Pharmaceutical Sciences, The University of Houston, 1441 Moursund Street, Houston TX 77030, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, Department of Pharmacological and Pharmaceutical Sciences, The University of Houston, 1441 Moursund Street, Houston TX 77030, Department of Pharmaceutical and Environmental Sciences, Texas Southern University, 3100 Cleburne Street, Houston TX 77004



Read Full-Text article